对于MSH6病原型变体载体的癌症风险
Anne-Sophie van der Werf-'t Lam1, James G Dowty2, Morrison Italia2
1Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands.
概括
患有MSH6致病变体 (PVs) 的人面临着结直肠和子宫内膜癌以及其他恶性瘤的风险增加. 这些发现支持个性化癌症查和MSH6相关林奇综合征的风险降低策略.
科学领域:
- 遗传学和基因组学 在
- 在瘤学瘤学.
- 遗传性癌症综合征 遗传性癌症综合征
背景情况:
- 林奇综合征 (LS) 是一种遗传性癌症综合征,与DNA不匹配修复基因致病变体 (PVs) 相关,包括MSH6.
- 与MSH6相关的LS (MSH6-LS) 增加了癌症风险,但准确的估计,特别是对于非结肠直肠癌,是不确定的,阻碍了个性化临床指导.
研究的目的:
- 改进携带致病性或可能致病性MSH6变种的个体的癌症风险估计.
- 为MSH6 PV载体提供特定年龄和性别的风险数据,以告知临床管理.
主要方法:
- 对来自360个荷兰家庭的1117个MSH6光伏载体进行了回顾性队列研究 (1995-2020).
- 通过医疗记录确认的癌症诊断;使用隔离分析计算的年龄和性别特定的累积风险 (CR) 和危险比率 (HR),以确定偏差进行调整.
主要成果:
- 到80岁时,男性的累积CRC风险为36%,女性为21%. 在女性中,子宫内膜癌CR为23%.
- 卵巢 (6.4%),泌尿道 (男性10.1%,女性4.1%) 和胆道癌 (男性4.9%,女性4.2%) 的终身风险增加.
- 没有前列腺或乳腺癌的风险增加;40岁时CRC风险低 (男性0.2%,女性0.9%).
结论:
- 对MSH6 PV载体的精细,年龄和性别特定的风险估计提高了对MSH6-相关LS的理解.
- 这些估计支持量身定制的监测策略,包括延迟CRC查和针对女性进行风险降低手术的个性化咨询.
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